Parameters governing exhaustion of rare T cell-independent neutralizing IgM-producing B cells after LCMV infection

The late appearance of neutralizing antibodies (nAb) against lymphocytic choriomeningitis virus (LCMV) has been attributed to various factors including immunopathology, low frequency of high-affinity specific B cells and competition by nonspecific polyclonal B cell activation. To investigate the activation of LCMV-nAb-producing B cells early following infection, we performed adoptive transfers of LCMV-specific B cells into WT recipients. By modulating parameters such as viral load, number of specific B cells and presence of T cell help, we found that a high antigen-to-B cell ratio led to normal IgM responses. IgG and memory responses, however, were impaired as most nAb-producing B cells rapidly terminally differentiated into short-lived IgM plasma cells. Lowering the antigen-to-B cell ratio, or increasing the level of T cell help, could rescue the class-switched antibody response. Upon infection, a low frequency of LCMV-nAb-producing B cells, as observed in WT mice, results in a high antigen-to-B cell ratio and is likely to lead to terminal differentiation - and elimination - of these rare B cells.